Significant events and approaches for the overall study
following participant enrollment, but prior to group assignment

89 participants enrolled; 42 randomized and treated with study drug. 47 not randomized for following reasons: 3 withdrew consent, 38 no longer met study criteria, 6 had other reasons. Treatment was administered on Day 1 of each period after fast of 10 hours; Washout began after single dose in the period and was for at least 6 days.

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin From a Single Dose of Dapagliflozin Versus Cmax of Dapagliflozin From Co-administered Saxagliptin Plus Dapagliflozin - Pharmacokinetic Evaluable Population [ Time Frame: Day 1 (0 h to 60 h post dose) in each period ]

Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity [AUC(INF)] of Dapagliflozin From a Single Dose of Dapagliflozin Versus AUC (INF) of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus AUC(0-T) for Dapagliflozin When Co-administered With 5 mg Saxagliptin [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Maximum Observed Concentration (Cmax) of a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

AUC(0-T) of Saxagliptin From Single Dose 5 mg Saxagliptin Versus AUC(0-T) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

AUC(INF) of Saxagliptin From a Single Dose of 5 mg Saxagliptin Versus AUC(INF) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus Tmax of Dapagliflozin When Co-administered With 5 mg Saxagliptin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Half-life (T-HALF) of Dapagliflozin From a Single Dose of Dapagliflozin Versus T-Half of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Cmax of 5-Hydroxy (5-OH) Saxagliptin From a Single Dose Saxagliptin Versus Cmax of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

AUC(0-T) of 5-OH Saxagliptin From Single Dose Saxagliptin Versus AUC(0-T) of 5-OH From Saxagliptin Co-administered With Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

AUC(INF) of 5-OH Saxagliptin From a Single Dose Saxagliptin Versus AUC(INF) of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Cmax of the Saxagliptin Total Active Moiety From a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

AUC(INF) and AUC(0-T) of the Saxagliptin Total Active Moiety From a Single Dose 5 mg Saxagliptin Versus AUC(INF) and AUC(0-T) of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population

Measure Description

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin and 5-OH by LC-MS/MS using a validated method. Tmax was derived from the plasma concentration versus time profile for study drug and was measured in hours (h). Saxagliptin was the drug, 5-OH saxagliptin was the metabolite, and Saxagliptin total Active Moiety was molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin.

Time Frame

Day 1 (0h to 60h post dose) in each period

Safety Issue

No

Population Description

Explanation of how the number of participants for analysis was determined.
Includes whether analysis was per protocol, intention to treat, or another method.
Also provides relevant details such as imputation technique, as appropriate.

PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

Reporting Groups

Description

5 mg Saxagliptin

Treatment A: Single saxagliptin 5mg, Tablet, Oral.

5 mg Saxagliptin + 10 mg Dapagliflozin

Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.

Measured Values

5 mg Saxagliptin

5 mg Saxagliptin + 10 mg Dapagliflozin

Participants Analyzed [Units: Participants]

42

42

Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population [Units: h]Median (Full Range)

Tmax of Saxagliptin

0.50
(0.50 to 2.00)

1.00
(0.50 to 2.00)

Tmax of 5-OH Saxagliptin

1.50
(1.00 to 2.00)

1.50
(1.00 to 3.00)

Tmax of Saxagliptin Total Active Moiety

1.00
(0.50 to 2.00)

1.00
(0.50 to 2.00)

No statistical analysis provided for Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population

16. Secondary:

Half-life (T-HALF) of Saxagliptin, and 5-OH Saxagliptin From Single Dose 5 mg Saxagliptin Versus T-HALF of Saxagliptin and 5-OH From Co-administered Saxagliptin With 10 mg Dapagliflozin - PK Evaluable Population [ Time Frame: Day 1 (0h to 60h post dose) in each period ]

Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable [ Time Frame: Day 1 (0h to 60h post dose) in each period ]